Central Laboratory of Pathology, Department of Pathology and Molecular Oncology, University Hospital of Nice-Côte d'Azur University, Nice, France.
Department of Pathology, Armand Trousseau Hospital, APHP, Paris, France.
Genes Chromosomes Cancer. 2022 Dec;61(12):734-739. doi: 10.1002/gcc.23091. Epub 2022 Aug 31.
Most available molecular data on pancreatic acinar cell carcinoma (PACC) are provided by studies of adult cases. BRAF, RAF1, or RET rearrangements have been described in approximately 30% of cases. To the best of our knowledge, only seven cases with molecular data have been reported in pediatric PACC. We report here the comprehensive study of a pancreatic-type ACC from a 6-year-old patient. We detected an AGAP3::BRAF fusion. This result showing a BRAF rearrangement demonstrates a molecular link between adult and pediatric PACC. Moreover, it identifies AGAP3, a gene located at 7q36.1 that encodes a major component of the N-methyl-d-aspartate (NMDA) receptor signaling complex, as a partner gene of BRAF. The variability of BRAF partners is consistent with a driver role of BRAF alterations in PACC. The identification of such alterations is noteworthy for considering the use of MEK inhibitors in metastatic cases. We did not detect associated genomic instability. The better outcome of pediatric cases might be related to their stable genomic background.
大多数关于胰腺腺泡细胞癌（PACC）的分子数据都是通过对成人病例的研究提供的。约 30%的病例中存在 BRAF、RAF1 或 RET 重排。据我们所知，仅有 7 例儿科 PACC 有分子数据报道。我们在此报告一例来自 6 岁患者的胰腺型 ACC 的综合研究。我们检测到 AGAP3::BRAF 融合。这一 BRAF 重排的结果表明，成人和儿科 PACC 之间存在分子联系。此外，它确定了 AGAP3，一种位于 7q36.1 上的基因，编码 N-甲基-D-天冬氨酸（NMDA）受体信号复合物的主要组成部分，是 BRAF 的伙伴基因。BRAF 伙伴的变异性与 PACC 中 BRAF 改变的驱动作用一致。鉴定这种改变对于考虑在转移性病例中使用 MEK 抑制剂具有重要意义。我们没有检测到相关的基因组不稳定性。儿科病例的较好预后可能与它们稳定的基因组背景有关。
